Redes Sociales creativas para portfolios. El caso de Behance en España

El presente trabajo trata sobre las comunidades creativas y cómo se utilizan como herramienta para exponer los portfolios, con la intención de tener una repercusión en el sector. El objetivo final es que los demás usuarios te valoren, para así poder, en la mayoría de casos, acceder a un empleo afín a sus dotes creativas. Se ha hecho un recorrido por las diferentes redes sociales creativas, más utilizadas por este tipo de usuarios, haciendo especial hincapié en la plataforma Behance, considerada como una de las más influyentes en el sector de la creatividad. Éstas plataformas acaban siendo una herramienta fundamental para cualquier creativo, profesional que pretenda darse a conocer más allá de su ámbito habitual y poder optar a expandirse creando una marca personal fuerte y duradera. En dicha comunidad se han estudiado los perfiles más valorados a nivel nacional en España, y se ha llevado a cabo un análisis de estos, tanto del perfil profesional como de los trabajos que mayor número de valoraciones positivas reúnen. Para ello también hemos llevado a cabo un cuestionario que le hemos planteado a diversos diseñadores gráficos, todos con una valoración muy positiva en Behance, comunidad creativa por excelencia, en la que la mayoría de diseñadores, creativos, ilustradores y artistas, muestran sus trabajos y el proceso de creación de estos.Grado en Publicidad y Relaciones Pública

Proyecto de creación y adecuación de una senda forestal interpretativa en el término municipal de Santurde de Rioja (La Rioja)

Este proyecto tiene como finalidad la creación y adecuación de una senda forestal interpretativa en el MUP 076 de Santurde de Rioja (La Rioja). Consiste en una senda circular cuyo recorrido transcurre bordeando el barranco de Cansorros por sus dos márgenes. El punto más alto del recorrido, donde se habilitará una zona de mirador, nos ofrece vistas de la Sierra de la Demanda y el Alto Valle del Oja a sus pies. Uno de los objetivos del proyecto es dar a conocer la flora que predomina en la zona elegida y, para ello, se colocarán carteles informativos en ciertos puntos estratégicos de la senda, así como la señalización que sea necesaria para proporcionar un paseo cómodo y agradable a los visitantes de la zona. También se habilitará una zona de descanso, una de mirador y una de aparcamiento.Grado en Ingeniería Forestal y del Medio Natura

Factores que contribuyen a la obesidad

Introducción: La obesidad es un importante problema de salud pública que conlleva múltiples comorbilidades y deterioro de la calidad de vida. Objetivo: Identificar los factores de riesgo que influyen en la aparición de sobrepeso y obesidad en adolescentes de 13 a 15 años de los Juniors Flor de Neu de Alcoy (Alicante). Material y métodos: Estudio observacional, descriptivo, longitudinal y analítico realizado con una muestra de 40 adolescentes entre 13 y 15 años, entre noviembre de 2019 y marzo de 2020. Se estudiaron variables sociodemográficas, de hábitos y frecuencia alimentarios, de estilo de vida, antropométricas, de creencias, de calidad de sueño y clínicas. Para todas las pruebas se aceptó un nivel de significación inferior a 0,05 en contraste bilateral. Resultados: Analizamos a 40 adolescentes con una edad media de 14,13 años (DT=0,46) donde el 47,5% eran varones y el 52,5% mujeres. Encontramos una prevalencia del 12,5% de sobrepeso y del 2,5% de obesidad. La presión arterial sistólica fue 9,80 mmHg mayor (IC95% 0,43-19,18) y la diastólica 11,72 mmHg mayor en el grupo de sobrepeso/obesidad (IC95% 4,0-19,43). Como alimentos protectores para la obesidad hallamos las verduras, pescados y huevos; En cambio, la fruta en almíbar y embutidos suponen un riesgo para la obesidad. Conclusiones: Se encontró relación entre el sobrepeso y el aumento de la presión arterial, no fue así entre la calidad y cantidad de sueño con el exceso de peso. Las medidas antropométricas tras de la intervención de EpS se han visto disminuidas salvo en los casos de masa magra y pliegue suprailíaco.Introduction: Obesity is a major public health problem which origin is multifactorial. Objectives: To identify the risk factors that influence the appearance of overweight and obesity in 13-15-year-old students of the Flor de Neu Juniors. Material and methods: Observational, descriptive, longitudinal and analytical multivariate study. Data were collected from 39 children between 13 and 15 years old belonging to the Juniors Flor de Neu Center in Alcoy, Alicante (Spain) between November 2019 and March 2020. Anthropometric, food frequency, beliefs and social variables were collected by a questionnaire. Results: We analyzed 40 adolescents with an average age of 14.13 years (SD=0.46) where 47.5% were male and 52.5% female. We found a prevalence of 12.5% overweight and 2.5% obesity. The systolic blood pressure is 9.80 mmHg higher (IC95% 0.43-19.18) and the diastolic is 11.72 mmHg higher in the overweight/obesity group (IC95% 4.0- 19.43). Vegetables, fish or eggs are protective foods for obesity, whereas foods such as fruit in syrup, industrial products and sausages pose a risk for overweight. Conclusions: A relationship has been found between overweight and increased blood pressure levels. We did not determine a relationship between the quality and quantity of sleep with overweight and obesity. Anthropometric measurements after EpS intervention have been decreased except in the cases of lean mass and suprailiac crease.Enfermerí

A 1-to-2 demultiplexer hybrid nanocarrier for cargo delivery and activation

[EN] A biocomputing strategy implemented in hybrid nanocarriers for controlled cargo delivery is described. The nanodevice consists of enzyme-functionalized Janus Au-mesoporous silica nanoparticles, which behave as an electronic demultiplexer (DEMUX). The nanocarrier is capable of reading molecular information from the environment (lactose) and selecting one of two possible outputs (galactose production or 4-methylumbellilferone release and activation) depending on the presence of an addressing input NAD(+).The authors wish to thank the Spanish Government (projects RTI2018-100910-B-C41 (MCUI/AEI/FEDER, UE), CTQ2017-87954-P), the Generalitat Valenciana (PROMETEO 2018/024), the Comunidad de Madrid (IND2017/BMD-7642) and CIBER-BBN (NANOCOMMUNITY project) for support.De Luis-Fernández, B.; García-Fernández, A.; Llopis-Lorente, A.; Villalonga, R.; Sancenón Galarza, F.; Martínez-Máñez, R. (2020). A 1-to-2 demultiplexer hybrid nanocarrier for cargo delivery and activation. Chemical Communications. 56(69):9974-9977. https://doi.org/10.1039/d0cc03803bS997499775669Soto, F., & Chrostowski, R. (2018). Frontiers of Medical Micro/Nanorobotics: in vivo Applications and Commercialization Perspectives Toward Clinical Uses. Frontiers in Bioengineering and Biotechnology, 6. doi:10.3389/fbioe.2018.00170Zhang, X., Chen, L., Lim, K. H., Gonuguntla, S., Lim, K. W., Pranantyo, D., … Soh, S. (2019). The Pathway to Intelligence: Using Stimuli‐Responsive Materials as Building Blocks for Constructing Smart and Functional Systems. Advanced Materials, 31(11), 1804540. doi:10.1002/adma.201804540Mailloux, S., & Katz, E. (2014). Biocomputing, Biosensing and Bioactuation Based on Enzyme Biocatalyzed Reactions. Biocatalysis, 1(1). doi:10.2478/boca-2014-0002Katz, E. (2018). Boolean Logic Gates Realized with Enzyme‐catalyzed Reactions – Unusual Look at Usual Chemical Reactions. ChemPhysChem, 20(1), 9-22. doi:10.1002/cphc.201800900Erbas-Cakmak, S., Kolemen, S., Sedgwick, A. C., Gunnlaugsson, T., James, T. D., Yoon, J., & Akkaya, E. U. (2018). Molecular logic gates: the past, present and future. Chemical Society Reviews, 47(7), 2228-2248. doi:10.1039/c7cs00491eSu, H., Xu, J., Wang, Q., Wang, F., & Zhou, X. (2019). High-efficiency and integrable DNA arithmetic and logic system based on strand displacement synthesis. Nature Communications, 10(1). doi:10.1038/s41467-019-13310-2Orbach, R., Willner, B., & Willner, I. (2015). Catalytic nucleic acids (DNAzymes) as functional units for logic gates and computing circuits: from basic principles to practical applications. Chemical Communications, 51(20), 4144-4160. doi:10.1039/c4cc09874aArugula, M. A., Bocharova, V., Halámek, J., Pita, M., & Katz, E. (2010). Enzyme-Based Multiplexer and Demultiplexer. The Journal of Physical Chemistry B, 114(15), 5222-5226. doi:10.1021/jp101101bAndréasson, J., Straight, S. D., Bandyopadhyay, S., Mitchell, R. H., Moore, T. A., Moore, A. L., & Gust, D. (2007). A Molecule-Based 1:2 Digital Demultiplexer. The Journal of Physical Chemistry C, 111(38), 14274-14278. doi:10.1021/jp074429pTuran, I. S., Gunaydin, G., Ayan, S., & Akkaya, E. U. (2018). Molecular demultiplexer as a terminator automaton. Nature Communications, 9(1). doi:10.1038/s41467-018-03259-zOrbach, R., Remacle, F., Levine, R. D., & Willner, I. (2014). DNAzyme-based 2:1 and 4:1 multiplexers and 1:2 demultiplexer. Chemical Science, 5(3), 1074. doi:10.1039/c3sc52752bLuo, C., Sun, J., Sun, B., & He, Z. (2014). Prodrug-based nanoparticulate drug delivery strategies for cancer therapy. Trends in Pharmacological Sciences, 35(11), 556-566. doi:10.1016/j.tips.2014.09.008Moreira, J., Hamraz, M., Abolhassani, M., Bigan, E., Pérès, S., Paulevé, L., … Schwartz, L. (2016). The Redox Status of Cancer Cells Supports Mechanisms behind the Warburg Effect. Metabolites, 6(4), 33. doi:10.3390/metabo6040033Adekola, K., Rosen, S. T., & Shanmugam, M. (2012). Glucose transporters in cancer metabolism. Current Opinion in Oncology, 24(6), 650-654. doi:10.1097/cco.0b013e328356da72Jerez, G., Kaufman, G., Prystai, M., Schenkeveld, S., & Donkor, K. K. (2009). Determination of thermodynamic pKavalues of benzimidazole and benzimidazole derivatives by capillary electrophoresis. Journal of Separation Science, 32(7), 1087-1095. doi:10.1002/jssc.200800482Guo, Z. (2017). The modification of natural products for medical use. Acta Pharmaceutica Sinica B, 7(2), 119-136. doi:10.1016/j.apsb.2016.06.003Llopis-Lorente, A., de Luis, B., García-Fernández, A., Jimenez-Falcao, S., Orzáez, M., Sancenón, F., … Martínez-Máñez, R. (2018). Hybrid Mesoporous Nanocarriers Act by Processing Logic Tasks: Toward the Design of Nanobots Capable of Reading Information from the Environment. ACS Applied Materials & Interfaces, 10(31), 26494-26500. doi:10.1021/acsami.8b05920Llopis-Lorente, A., Díez, P., Sánchez, A., Marcos, M. D., Sancenón, F., Martínez-Ruiz, P., … Martínez-Máñez, R. (2017). Interactive models of communication at the nanoscale using nanoparticles that talk to one another. Nature Communications, 8(1). doi:10.1038/ncomms15511Tregubov, A. A., Nikitin, P. I., & Nikitin, M. P. (2018). Advanced Smart Nanomaterials with Integrated Logic-Gating and Biocomputing: Dawn of Theranostic Nanorobots. Chemical Reviews, 118(20), 10294-10348. doi:10.1021/acs.chemrev.8b0019

Regulation of the Yeast Hxt6 Hexose Transporter by the Rod1 α-Arrestin, the Snf1 Protein Kinase, and the Bmh2 14-3-3 Protein

[EN] Cell viability requires adaptation to changing environmental conditions. Ubiquitin-mediated endocytosis plays a crucial role in this process, because it provides a mechanism to remove transport proteins from the membrane. Arrestin-related trafficking proteins are important regulators of the endocytic pathway in yeast, facilitating selective ubiquitylation of target proteins by the E3 ubiquitin ligase, Rsp5. Specifically, Rod1 (Art4) has been reported to regulate the endocytosis of both the Hxt1, Hxt3, and Hxt6 glucose transporters and the Jen1 lactate transporter. Also, the AMP kinase homologue, Snf1, and 14-3-3 proteins have been shown to regulate Jen1 via Rod1. Here, we further characterized the role of Rod1, Snf1, and 14-3-3 in the signal transduction route involved in the endocytic regulation of the Hxt6 high affinity glucose transporter by showing that Snf1 interacts specifically with Rod1 and Rog3 (Art7), that the interaction between the Bmh2 and several arrestin-related trafficking proteins may be modulated by carbon source, and that both the 14-3-3 protein Bmh2 and the Snf1 regulatory domain interact with the arrestin-like domain containing the N-terminal half of Rod1 (amino acids 1-395). Finally, using both co-immunoprecipitation and bimolecular fluorescence complementation, we demonstrated the interaction of Rod1 with Hxt6 and showed that the localization of the Rod1-Hxt6 complex at the plasma membrane is affected by carbon source and is reduced upon overexpression of SNF1 and BMH2.Supported by a predoctoral fellowship from the Polytechnic University of Valencia.Llopis Torregrosa, V.; Ferri-Blazquez, A.; Adam-Artigues, A.; Deffontaines, E.; Van Heusden, GPH.; Yenush, L. (2016). Regulation of the Yeast Hxt6 Hexose Transporter by the Rod1 α-Arrestin, the Snf1 Protein Kinase, and the Bmh2 14-3-3 Protein. Journal of Biological Chemistry. 291(29):14973-14985. https://doi.org/10.1074/jbc.M116.733923S149731498529129Mulet, J. M., Llopis-Torregrosa, V., Primo, C., Marqués, M. C., & Yenush, L. (2013). Endocytic regulation of alkali metal transport proteins in mammals, yeast and plants. Current Genetics, 59(4), 207-230. doi:10.1007/s00294-013-0401-2Hein, C., Springael, J.-Y., Volland, C., Haguenauer-Tsapis, R., & Andre, B. (1995). NPI1, an essential yeast gene involved in induced degradation of Gap1 and Fur4 permeases, encodes the Rsp5 ubiquitin-protein ligase. Molecular Microbiology, 18(1), 77-87. doi:10.1111/j.1365-2958.1995.mmi_18010077.xBabst, M., Katzmann, D. J., Estepa-Sabal, E. J., Meerloo, T., & Emr, S. D. (2002). Escrt-III. Developmental Cell, 3(2), 271-282. doi:10.1016/s1534-5807(02)00220-4Babst, M., Katzmann, D. J., Snyder, W. B., Wendland, B., & Emr, S. D. (2002). Endosome-Associated Complex, ESCRT-II, Recruits Transport Machinery for Protein Sorting at the Multivesicular Body. Developmental Cell, 3(2), 283-289. doi:10.1016/s1534-5807(02)00219-8Katzmann, D. J., Babst, M., & Emr, S. D. (2001). Ubiquitin-Dependent Sorting into the Multivesicular Body Pathway Requires the Function of a Conserved Endosomal Protein Sorting Complex, ESCRT-I. Cell, 106(2), 145-155. doi:10.1016/s0092-8674(01)00434-2Lauwers, E., Erpapazoglou, Z., Haguenauer-Tsapis, R., & André, B. (2010). The ubiquitin code of yeast permease trafficking. Trends in Cell Biology, 20(4), 196-204. doi:10.1016/j.tcb.2010.01.004Lin, C. H., MacGurn, J. A., Chu, T., Stefan, C. J., & Emr, S. D. (2008). Arrestin-Related Ubiquitin-Ligase Adaptors Regulate Endocytosis and Protein Turnover at the Cell Surface. Cell, 135(4), 714-725. doi:10.1016/j.cell.2008.09.025Aubry, L., & Klein, G. (2013). True Arrestins and Arrestin-Fold Proteins. The Molecular Biology of Arrestins, 21-56. doi:10.1016/b978-0-12-394440-5.00002-4Hatakeyama, R., Kamiya, M., Takahara, T., & Maeda, T. (2010). Endocytosis of the Aspartic Acid/Glutamic Acid Transporter Dip5 Is Triggered by Substrate-Dependent Recruitment of the Rsp5 Ubiquitin Ligase via the Arrestin-Like Protein Aly2. Molecular and Cellular Biology, 30(24), 5598-5607. doi:10.1128/mcb.00464-10Nikko, E., Sullivan, J. A., & Pelham, H. R. B. (2008). Arrestin-like proteins mediate ubiquitination and endocytosis of the yeast metal transporter Smf1. EMBO reports, 9(12), 1216-1221. doi:10.1038/embor.2008.199Nikko, E., & Pelham, H. R. B. (2009). Arrestin-Mediated Endocytosis of Yeast Plasma Membrane Transporters. Traffic, 10(12), 1856-1867. doi:10.1111/j.1600-0854.2009.00990.xMacGurn, J. A., Hsu, P.-C., Smolka, M. B., & Emr, S. D. (2011). TORC1 Regulates Endocytosis via Npr1-Mediated Phosphoinhibition of a Ubiquitin Ligase Adaptor. Cell, 147(5), 1104-1117. doi:10.1016/j.cell.2011.09.054Merhi, A., & Andre, B. (2012). Internal Amino Acids Promote Gap1 Permease Ubiquitylation via TORC1/Npr1/14-3-3-Dependent Control of the Bul Arrestin-Like Adaptors. Molecular and Cellular Biology, 32(22), 4510-4522. doi:10.1128/mcb.00463-12O’Donnell, A. F., Huang, L., Thorner, J., & Cyert, M. S. (2013). A Calcineurin-dependent Switch Controls the Trafficking Function of α-Arrestin Aly1/Art6. Journal of Biological Chemistry, 288(33), 24063-24080. doi:10.1074/jbc.m113.478511O’Donnell, A. F., McCartney, R. R., Chandrashekarappa, D. G., Zhang, B. B., Thorner, J., & Schmidt, M. C. (2014). 2-Deoxyglucose Impairs Saccharomyces cerevisiae Growth by Stimulating Snf1-Regulated and α-Arrestin-Mediated Trafficking of Hexose Transporters 1 and 3. Molecular and Cellular Biology, 35(6), 939-955. doi:10.1128/mcb.01183-14Becuwe, M., Vieira, N., Lara, D., Gomes-Rezende, J., Soares-Cunha, C., Casal, M., … Léon, S. (2012). A molecular switch on an arrestin-like protein relays glucose signaling to transporter endocytosis. The Journal of Cell Biology, 196(2), 247-259. doi:10.1083/jcb.201109113Alvaro, C. G., Aindow, A., & Thorner, J. (2016). Differential Phosphorylation Provides a Switch to Control How α-Arrestin Rod1 Down-regulates Mating Pheromone Response inSaccharomyces cerevisiae. Genetics, 203(1), 299-317. doi:10.1534/genetics.115.186122Alvaro, C. G., O’Donnell, A. F., Prosser, D. C., Augustine, A. A., Goldman, A., Brodsky, J. L., … Thorner, J. (2014). Specific  -Arrestins Negatively Regulate Saccharomyces cerevisiae Pheromone Response by Down-Modulating the G-Protein-Coupled Receptor Ste2. Molecular and Cellular Biology, 34(14), 2660-2681. doi:10.1128/mcb.00230-14Shinoda, J., & Kikuchi, Y. (2007). Rod1, an arrestin-related protein, is phosphorylated by Snf1-kinase in Saccharomyces cerevisiae. Biochemical and Biophysical Research Communications, 364(2), 258-263. doi:10.1016/j.bbrc.2007.09.134Ichimura, T., Yamamura, H., Sasamoto, K., Tominaga, Y., Taoka, M., Kakiuchi, K., … Isobe, T. (2005). 14-3-3 Proteins Modulate the Expression of Epithelial Na+Channels by Phosphorylation-dependent Interaction with Nedd4-2 Ubiquitin Ligase. Journal of Biological Chemistry, 280(13), 13187-13194. doi:10.1074/jbc.m412884200Bhalla, V., Daidié, D., Li, H., Pao, A. C., LaGrange, L. P., Wang, J., … Pearce, D. (2005). Serum- and Glucocorticoid-Regulated Kinase 1 Regulates Ubiquitin Ligase Neural Precursor Cell-Expressed, Developmentally Down-Regulated Protein 4-2 by Inducing Interaction with 14-3-3. Molecular Endocrinology, 19(12), 3073-3084. doi:10.1210/me.2005-0193Jiang, R., & Carlson, M. (1996). Glucose regulates protein interactions within the yeast SNF1 protein kinase complex. Genes & Development, 10(24), 3105-3115. doi:10.1101/gad.10.24.3105Proszynski, T. J., Klemm, R. W., Gravert, M., Hsu, P. P., Gloor, Y., Wagner, J., … Walch-Solimena, C. (2005). A genome-wide visual screen reveals a role for sphingolipids and ergosterol in cell surface delivery in yeast. Proceedings of the National Academy of Sciences, 102(50), 17981-17986. doi:10.1073/pnas.0509107102MacGurn, J. A., Hsu, P.-C., & Emr, S. D. (2012). Ubiquitin and Membrane Protein Turnover: From Cradle to Grave. Annual Review of Biochemistry, 81(1), 231-259. doi:10.1146/annurev-biochem-060210-093619Becuwe, M. , and Léon, S. (2014) Integrated control of transporter endocytosis and recycling by the arrestin-related protein Rod1 and the ubiquitin ligase Rsp5. Elife 3, 03307Alvarez, C. E. (2008). On the origins of arrestin and rhodopsin. BMC Evolutionary Biology, 8(1), 222. doi:10.1186/1471-2148-8-222Chutkow, W. A., Patwari, P., Yoshioka, J., & Lee, R. T. (2007). Thioredoxin-interacting Protein (Txnip) Is a Critical Regulator of Hepatic Glucose Production. Journal of Biological Chemistry, 283(4), 2397-2406. doi:10.1074/jbc.m708169200Sheth, S. S., Castellani, L. W., Chari, S., Wagg, C., Thipphavong, C. K., Bodnar, J. S., … Lusis, A. J. (2004). Thioredoxin-interacting protein deficiency disrupts the fasting-feeding metabolic transition. Journal of Lipid Research, 46(1), 123-134. doi:10.1194/jlr.m400341-jlr200Bodnar, J. S., Chatterjee, A., Castellani, L. W., Ross, D. A., Ohmen, J., Cavalcoli, J., … Lusis, A. J. (2001). Positional cloning of the combined hyperlipidemia gene Hyplip1. Nature Genetics, 30(1), 110-116. doi:10.1038/ng811Parikh, H., Carlsson, E., Chutkow, W. A., Johansson, L. E., Storgaard, H., Poulsen, P., … Mootha, V. K. (2007). TXNIP Regulates Peripheral Glucose Metabolism in Humans. PLoS Medicine, 4(5), e158. doi:10.1371/journal.pmed.0040158Yoshioka, J., Imahashi, K., Gabel, S. A., Chutkow, W. A., Burds, A. A., Gannon, J., … Lee, R. T. (2007). Targeted Deletion of Thioredoxin-Interacting Protein Regulates Cardiac Dysfunction in Response to Pressure Overload. Circulation Research, 101(12), 1328-1338. doi:10.1161/circresaha.106.160515Andres, A. M., Ratliff, E. P., Sachithanantham, S., & Hui, S. T. (2011). Diminished AMPK signaling response to fasting in thioredoxin-interacting protein knockout mice. FEBS Letters, 585(8), 1223-1230. doi:10.1016/j.febslet.2011.03.042Wu, N., Zheng, B., Shaywitz, A., Dagon, Y., Tower, C., Bellinger, G., … Cantley, L. C. (2013). AMPK-Dependent Degradation of TXNIP upon Energy Stress Leads to Enhanced Glucose Uptake via GLUT1. Molecular Cell, 49(6), 1167-1175. doi:10.1016/j.molcel.2013.01.035Patwari, P., Chutkow, W. A., Cummings, K., Verstraeten, V. L. R. M., Lammerding, J., Schreiter, E. R., & Lee, R. T. (2009). Thioredoxin-independent Regulation of Metabolism by the α-Arrestin Proteins. Journal of Biological Chemistry, 284(37), 24996-25003. doi:10.1074/jbc.m109.018093Paumi, C. M., Menendez, J., Arnoldo, A., Engels, K., Iyer, K. R., Thaminy, S., … Stagljar, I. (2007). Mapping Protein-Protein Interactions for the Yeast ABC Transporter Ycf1p by Integrated Split-Ubiquitin Membrane Yeast Two-Hybrid Analysis. Molecular Cell, 26(1), 15-25. doi:10.1016/j.molcel.2007.03.011Zonneveld, B. J. M. (1986). Cheap and simple yeast media. Journal of Microbiological Methods, 4(5-6), 287-291. doi:10.1016/0167-7012(86)90040-0Mayordomo, I., Regelmann, J., Horak, J., & Sanz, P. (2003). Saccharomyces cerevisiae 14-3-3 proteins Bmh1 and Bmh2 participate in the process of catabolite inactivation of maltose permease. FEBS Letters, 544(1-3), 160-164. doi:10.1016/s0014-5793(03)00498-8Zahrádka, J., van Heusden, G. P. H., & Sychrová, H. (2012). Yeast 14-3-3 proteins participate in the regulation of cell cation homeostasis via interaction with Nha1 alkali-metal-cation/proton antiporter. Biochimica et Biophysica Acta (BBA) - General Subjects, 1820(7), 849-858. doi:10.1016/j.bbagen.2012.03.013Sung, M.-K., & Huh, W.-K. (2007). Bimolecular fluorescence complementation analysis system forin vivo detection of protein–protein interaction inSaccharomyces cerevisiae. Yeast, 24(9), 767-775. doi:10.1002/yea.1504Longtine, M. S., Mckenzie III, A., Demarini, D. J., Shah, N. G., Wach, A., Brachat, A., … Pringle, J. R. (1998). Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae. Yeast, 14(10), 953-961. doi:10.1002/(sici)1097-0061(199807)14:103.0.co;2-uBurd, C. G., & Emr, S. D. (1998). Phosphatidylinositol(3)-Phosphate Signaling Mediated by Specific Binding to RING FYVE Domains. Molecular Cell, 2(1), 157-162. doi:10.1016/s1097-2765(00)80125-2Yenush, L., Merchan, S., Holmes, J., & Serrano, R. (2005). pH-Responsive, Posttranslational Regulation of the Trk1 Potassium Transporter by the Type 1-Related Ppz1 Phosphatase. Molecular and Cellular Biology, 25(19), 8683-8692. doi:10.1128/mcb.25.19.8683-8692.2005Gaxiola, R., de Larrinoa, I. F., Villalba, J. M., & Serrano, R. (1992). A novel and conserved salt-induced protein is an important determinant of salt tolerance in yeast. The EMBO Journal, 11(9), 3157-3164. doi:10.1002/j.1460-2075.1992.tb05392.

Acetylcholine-responsive cargo release using acetylcholinesterase-capped nanomaterials

[EN] Mesoporous silica nanoparticles capped with acetylcholinesterase, through boronic ester linkages, selectively release an entrapped cargo in the presence of acetylcholine.The authors acknowledge financial support from the Spanish Government (MAT2015-64139-C4-1-R, MAT2015-64139-C4-4-R and AGL2015-70235-C2-2-R) and the Generalitat Valenciana (PROMETEO2018/024). T. Godoy-Reyes is grateful to Generalitat Valenciana for her Santiago Grisollía fellowship. A. García-Fernández is grateful to the Spanish Government for her FPU fellowshipGodoy-Reyes, TM.; Llopis-Lorente, A.; García-Fernández, A.; Gaviña, P.; Costero, AM.; Martínez-Máñez, R.; Sancenón Galarza, F. (2019). Acetylcholine-responsive cargo release using acetylcholinesterase-capped nanomaterials. Chemical Communications. 55(41):5785-5788. https://doi.org/10.1039/c9cc02602aS578557885541McCorry, L. K. (2007). Physiology of the Autonomic Nervous System. American Journal of Pharmaceutical Education, 71(4), 78. doi:10.5688/aj710478W. 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Sustained CHK2 activity, but not ATM activity, is critical to maintain a G1 arrest after DNA damage in untransformed cells

BACKGROUND: The G1 checkpoint is a critical regulator of genomic stability in untransformed cells, preventing cell cycle progression after DNA damage. DNA double-strand breaks (DSBs) recruit and activate ATM, a kinase which in turn activates the CHK2 kinase to establish G1 arrest. While the onset of G1 arrest is well understood, the specific role that ATM and CHK2 play in regulating G1 checkpoint maintenance remains poorly characterized. RESULTS: Here we examine the impact of ATM and CHK2 activities on G1 checkpoint maintenance in untransformed cells after DNA damage caused by DSBs. We show that ATM becomes dispensable for G1 checkpoint maintenance as early as 1h after DSB induction. In contrast, CHK2 kinase activity is necessary to maintain the G1 arrest, independently of ATM, ATR, and DNA-PKcs, implying that the G1 arrest is maintained in a lesion-independent manner. Sustained CHK2 activity is achieved through auto-activation and its acute inhibition enables cells to abrogate the G1-checkpoint and enter into S-phase. Accordingly, we show that CHK2 activity is lost in cells that recover from the G1 arrest, pointing to the involvement of a phosphatase with fast turnover. CONCLUSION: Our data indicate that G1 checkpoint maintenance relies on CHK2 and that its negative regulation is crucial for G1 checkpoint recovery after DSB induction.This research was funded by grants from MCIU/AEI/FEDER, UE (SAF2015-67562-R and RTI2018-097497-B-100) and Basque Government, Department of Education (IT1257-19) to A.M.Z., and Cancer Genomics Center Gravity Program (CGC.nl), Oncode Institute, Dutch Cancer Society (NKI 2014-6787) grants to R.H.M. I.G.-S. was supported with a postdoctoral fellowship from the Basque Country Government (Spain). J.V.-R. was supported by a postdoctoral fellowship from the University of the Basque Country (UPV/EHU)

Acute hydroxyurea-induced replication blockade results in replisome components disengagement from nascent DNA without causing fork collapse

During S phase, replication forks can encounter several obstacles that lead to fork stalling, which if persistent might result in fork collapse. To avoid this collapse and to preserve the competence to restart, cells have developed mechanisms that maintain fork stability upon replication stress. In this study, we aimed to understand the mechanisms involved in fork stability maintenance in non-transformed human cells by performing an isolation of proteins on nascent DNA-mass spectrometry analysis in hTERT-RPE cells under different replication stress conditions. Our results show that acute hydroxyurea-induced replication blockade causes the accumulation of large amounts of single-stranded DNA at the fork. Remarkably, this results in the disengagement of replisome components from nascent DNA without compromising fork restart. Notably, Cdc45-MCM-GINS helicase maintains its integrity and replisome components remain associated with chromatin upon acute hydroxyurea treatment, whereas replisome stability is lost upon a sustained replication stress that compromises the competence to restart

Hybrid Mesoporous Nanocarriers Act by Processing Logic Tasks: Toward the Design of Nanobots Capable of Reading Information from the Environment

[EN] Here, we present the design of smart nano-devices capable of reading molecular information from the environment and acting accordingly by processing Boolean logic tasks. As proof of concept, we prepared Au-mesoporous silica (MS) nanoparticles functionalized with the enzyme glucose dehydrogenase (GDH) on the Au surface and with supramolecular nanovalves as caps on the MS surface, which is loaded with a cargo (dye or drug). The nanodevice acts as an AND logic gate and reads information from the solution (presence of glucose and nicotinamide adenine dinucleotide (NADI), which results in cargo release. We show the possibility of coimmobilizing GDH and the enzyme urease on nanoparticles to mimic an INHIBIT logic gate, in which the AND gate is switched off by the presence of urea. We also show that such nanodevices can deliver cytotoxic drugs in cancer cells by recognizing intracellular NAD(+) and the presence of glucose.A.L.-L. is grateful to "La Caixa" Banking Foundation for his Ph.D. grant. A.G.-F. and B.de L. thank the Spanish government for FPU fellowships. The authors are grateful to the Spanish Government (MINECO Projects MAT2015-64139-C4-1, CTQ2014-58989-P, and CTQ2015-71936-REDT) and the Generalitat Valencia (Project PROMETEOII/2014/047 and PROMETEOII/2014/061) for support. The Comunidad de Madrid (S2013/MIT-3029, Programme NANOAVANSENS) is also gratefully acknowledged.Llopis-Lorente, A.; De Luis-Fernández, B.; García-Fernández, A.; Jiménez-Falcao, S.; Orzaez, M.; Sancenón Galarza, F.; Villalonga, R.... (2018). Hybrid Mesoporous Nanocarriers Act by Processing Logic Tasks: Toward the Design of Nanobots Capable of Reading Information from the Environment. ACS Applied Materials & Interfaces. 10(31):26494-26500. https://doi.org/10.1021/acsami.8b05920S2649426500103